Abstract
In a systematic effort to develop a dual-function intravaginal spermicide as well as a drug delivery vehicle against sexually transmitted pathogens, a submicron particle size (30-80 nm), lipophilic and spermicidal gel-microemulsion (viz GM-144) containing the pharmaceutical excipients propylene glycol, Captex 300, Cremophor EL, Phospholipon 90G, Rhodigel, Pluronic F-68, and sodium benzoate was formulated. GM-144 completely immobilized sperm in human or rabbit semen in less than 30 seconds. Therefore, the in vivo contraceptive potency of intravaginally applied GM-144 was compared in the standard rabbit model to those of the detergent spermicide, nonoxynol-9 (N-9)-containing formulation. Eighty-four ovulated New Zealand White rabbits in subgroups of 28 were artificially inseminated with and without intravaginal administration of GM-144 or 2% N-9 (Gynol II) formulation and allowed to complete term pregnancy. GM-144 showed remarkable contraceptive activity in the rigorous rabbit model. When compared with control, intravaginal administration of GM-144 and Gynol II resulted in 75% and 70.8% inhibition of fertility (P <.0001 versus control, Fisher's exact test), respectively. Thus, GM-144 as a vaginal contraceptive was as effective as the commercially available N-9 gel. In the rabbit vaginal irritation test, none of the 6 rabbits given daily intravaginal application of spermicidal GM-144 for 10 days developed epithelial ulceration, edema, leukocyte influx, or vascular congestion characteristic of inflammation (total score = 5). Therefore, GM-144 has the potential to become a clinically useful safe vaginal contraceptive and a vehicle for formulating lipophilic drugs used in reducing the risk of heterosexual transmission of sexually transmitted diseases.